tbuckley/cabot-search huggingface dataset:
Abstract 11125: Association of Interleukin-6 and Interleukin-18 With Global Cardiovascular Disease in Older Adults
Authors: Xiaoming Jia, Leo Buckley, Caroline Sun, Mahmoud Al Rifai, Bing Yu, VIJAY NAMBI, Salim S Virani, Elizabeth Selvin, Kuni Matsushita, Ron C Hoogeveen, Josef Coresh, Amil M Shah, Christie M Ballantyne
Journal: Circulation (2022)

Introduction: Increasing evidence suggest that inflammation plays an important role in chronic disease progression in the elderly, a process known as inflammaging. We assessed the associations of interleukin-6 (IL-6) and interleukin-18 (IL-18) with global cardiovascular disease (CVD), atrial fibrillation (AF) and death among older adults. Methods: Participants from Atherosclerosis Risk in Communities study visit 5 (2011-2013; mean age 75.4±5.1 years) with measurements of IL-6 and IL-18 were included (N=5672). Enzyme-linked immunosorbent assay was used to quantify IL-6 and IL-18. The associations of IL-6 and IL-18 (modeled continuously and categorically as tertiles) with coronary heart disease (CHD), ischemic stroke, heart failure (HF), global CVD (composite of CHD, stroke, and HF), AF, and all-cause death were assessed using Cox regression analyses. Results: Over a median follow-up of 7.2 years, 1235 global CVD events, 530 AF events and 1173 deaths occurred. Higher IL-6 and IL-18 levels were both associated with global CVD after adjustment for cardiovascular risk factors. The association between IL-6 and CVD remained significant after further adjustment for IL-18, while the association between IL-18 and CVD was no longer significant after adjustment for IL-6. IL-6 but not IL-18 was also associated with increased risk for CHD, HF, and AF after adjustments for cardiovascular risk factors and each other. Both IL-6 and IL-18 were associated with increased risk for all-cause death (Table). In categorical analysis, the top tertile of IL-6 was associated with increased risk for global CVD, AF and death using the lowest tertile as the reference group. Conclusion: Among older adults, both IL-6 and IL-18 were associated with global CVD and death. However, the association of IL-18 with CVD appears to be mediated by IL-6.
Abstract 11828: Contemporary Temporal Trends in Cardiovascular Events Among Elderly Patients Hospitalized With Autoimmune Disorders and Concomitant Recreational Cannabis Use
Authors: Nishanth Katukuri, Adil S Mohammed, Sai Gautham Kanagala, Priyatham Gurram, Mariam Ashfaque, Amara Sofia, Humaira Kauser, Qudsia Sayyeda, Satya Sai Venkata Lakshmi Arepalli, Avilash Mondal, Rupak Desai
Journal: Circulation (2022)

Background: The role of Cannabis in autoimmune diseases (AD) has been previously discussed due to its anti-inflammatory properties, however, cardiovascular events in elderly patients with AD are not well studied with habitual recreational cannabis usage or cannabis use disorder (CUD). Methods: We queried the National Inpatient Sample (2016-2019) for geriatric AD patients with vs. without CUD. Propensity score-matched analysis (1:1) was used to compare comorbidities, major adverse cardiac and cerebrovascular events [MACCE: all-cause mortality, acute myocardial infarction (AMI), cardiac arrest and acute ischemic stroke (AIS)], and healthcare resource utilization in the CUD vs. non-CUD cohort with AD. Results: Of 11350 elderly admissions with AD, propensity-matched cohorts consisted of 5675 patients with CUD (49.1% male) and without CUD (26.7% male). Both groups had comparable ages (median 69 years), racial groups (&gt;70% white), and income quartiles. CUD cohort showed higher rates of hypertension, PVD, smoking, alcohol abuse, drug abuse, depression, and prior MI (p&lt;0.005) compared to the non-CUD cohort. The CUD cohort had higher rate of transfers to other care facilities (2.6% vs. 1.9%, p≤0.001), prolonged hospital stays, and higher cost, the adjusted odds were not significant for MACCE (OR 1.22, 95%CI 0.88-1.69, p=0.24), all-cause mortality (OR 0.74, 95%CI 0.37-1.46, p=0.34), AMI (OR 1.52, 95%CI 0.95-2.43, p=0.08), AIS (OR 1.19, 95%CI 0.69-2.17, p=0.57), or cardiac arrest (OR 1.34, 95%CI 0.55-3.26, p=0.51), compared to non-CUD elderly AD cohort. The CUD cohort often had routine discharges (52.7% vs. 47.4%, p≤0.001) compared to the non-CUD cohort. Conclusions: This nationwide propensity-matched analysis did not reveal worse cardiovascular outcomes in older AD patients with CUD. Future large-scale prospective studies are needed to validate these findings and evaluate the long-term effects of medicinal/recreational cannabis usage in these individuals.
Abstract 11591: An Artificial Intelligence Approach in Predicting Subsequent Stroke or Death After Ischemic Stroke: Comparison With Conventional Statistical Methods and External Validation of iScore
Authors: Daniel Axford, Ferdous Sohel, Mohammed Yousufuddin
Journal: Circulation (2022)

Introduction: Machine learning models (MLM) hold promise for improved risk stratification and to guide personalized care. Hypothesis: MLM would outperform conventional statistical (CS) methods and existing iScore for predicting composite of recurrent stroke or death at 90 days and 3 years after ischemic stroke (IS) Methods: We built 3 MLM (random forest [RF], support vector machine [SVM], and extreme gradient boosting decision trees [XGBoost]) and two CS models (logistic regression [LR] and least absolute shrinkage and selection operator [LASSO]) to predict composite outcome at 90 days or 3 years after AIS in a retrospective cohort of 721 adults. The performance of these models was evaluated against the existing iScore to predict outcomes after AIS. Results: Composite outcome occurred in11% at 90 days and in 34% at 3 years after AIS. Performance metrics for predicting 90-day and 3-year composite outcome were comparable across all study models except SM LR. Measurements for the area under the receiver operating characteristic curve for each model in validation set was as follow. 1) 90-day prediction: 0.779 for RF, 0.771 for SVM, 0.772 for EXBOOST, 0.613 for LR, 0.811 for LASSO, and 0.720 for iScore; 2) 3-year prediction: 0.743 for RF, 0.777 for SVM, and 0.773 for EXBOOST, 0.724 for LR, 0.790 for LASSO, and 0.710 for iScore. Conclusions: ML-based algorithms did not improve prediction of composite outcome at 90 days or 3 years after AIS compared with CS-based LASSO. iScore was successfully validated and compared broadening its generalizability and applicability.
Abstract 11397: Circulating Human Metabolites Resulting From TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Hypocholesterolemic Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons From an Original ex vivo Clinical Trial
Authors: Fabien WAUQUIER, Cedric Langhi, line wittrant, Yolanda F Otero, Florian Le Joubioux, Thierry MAUGARD, VÃ©ronique ROUX, Nicolas MACIAN, gisele pickering, Maxime Bargetto, Murielle Cazaubiel, Sébastien PELTIER, Pascal Sirvent, Yohann Wittrant
Journal: Circulation (2022)

Introduction: TOTUM-070 is a patented polyphenol-rich compound which has shown hypocholesterolemic properties in preclinical studies. However, clinically validated approaches and further investigations on the mode of action at cellular level especially in humans are required for optimized care management. In this study, we designed an ex-vivo clinical innovative approach considering the metabolites produced by the digestive tract following the ingestion of TOTUM-070 in humans. Methods: Human serum was collected in healthy subjects before and following acute intake of 5g of TOTUM-070. Availability of circulating metabolites was confirmed and characterized by UPLC-MS. Human serum enriched with metabolites deriving from TOTUM-070 absorption was further incubated with human hepatocytes, pretreated or not with palmitate (250 μM). In such lipotoxic environment, hepatocyte behavior was monitored to determine whether and how TOTUM-070 metabolites may improve cholesterol metabolism in human. Results: In the presence of the human metabolites from TOTUM-070, human hepatocytes were protected from an induced lipotoxic stress. No effect on cell toxicity was detected in the presence of enriched sera. Hepatocyte protection was characterized by (1) the inhibition of both triglycerides (-41%, p&lt;0.001) and cholesterol (-50%, p&lt;0.001) storage, (2) a reduced de novo cholesterol synthesis (HMG-CoA reductase activity reduced by 44%, p&lt;0.001), (3) a lowered fatty acid synthase expression (p&lt;0.001), (4) the stimulation of the Lecithin Cholesterol Acyl Transferase (LCAT) activity (p&lt;0.05) and finally (5) a higher CYP7A1 expression (p&lt;0.05). All together, these data provide new biochemical insights into the mechanisms underlying, in humans, the beneficial impact of TOTUM-070 on lipid metabolism in liver cells. Conclusion: Using a pioneering clinical ex vivo approach considering the digestive processes of nutrients, we give clues on the role of circulating metabolites produced following TOTUM-070 intake in humans in hepatocyte protection.
Abstract 12185: Medication Changes And Reasons For No Medication Change Among Outpatients With Heart Failure With Reduced Ejection Fraction: Results From CHART-HF
Authors: Stephen J Greene, Hanna K Gaggin, Dominik Lautsch, Yan Song, James Signorovitch, Andra S Stevenson, Robert Blaustein, Mo Zhou, Javed Butler
Journal: Circulation (2022)

Introduction: Underuse and under-dosing of guideline-directed medical therapy (GDMT) for HFrEF in US outpatient practice is well documented. Yet changes to GDMT and clinician-reported reasons for not making medication changes are not well described. Methods: US cardiologists were recruited from the Schlesinger Group, a nationwide panel of physicians who participate in web-based surveys. The cardiologists conducted anonymized chart reviews of their own randomly selected patients meeting eligibility criteria. Eligible patients had HFrEF&lt;45% without end-stage kidney disease, and an outpatient cardiology visit between 2017-2019. For each index outpatient visit, cardiologists abstracted data on medication changes and reported their primary rationale for not making a change in each specific therapy. Results: Overall, 238 cardiologists participated and reviewed outpatient visits for 458 patients under their care (median age 64 years, 65% male). Before the index visit, proportions of patients not prescribed beta-blocker, MRA, ARNI, and SGLT2i were 17%, 58%, 72%, and 86%, respectively. Across medications, proportions of patients with medication initiation ranged from 5-11%, medication discontinuation from 0-11%, with variable rates of dose changes (Figure, Panel A). Among patients receiving medication, for each therapy, the most common clinician-reported reason for no medication change was patient clinical stability (43-57%). Other reasons for no medication change included already being at target dose (29-44% of cases), and perceived risk of intolerance (6-11%) (Figure, Panel B) . Conclusions: We observed relatively few medication changes made among these HFrEF patients. Patient stability and perceived risk of intolerance were frequently cited by cardiologists as reasons for not making guideline-directed medication changes, suggesting clinical inertia as a major barrier to closing gaps in GDMT.
Abstract 11701: Generalizability of the Victoria Trial and the US FDA Label for Vericiguat to Patients Hospitalized for Heart Failure With Reduced Ejection Fraction in the United States
Authors: Mohammad S Khan, Haolin Xu, Gregg C Fonarow, Dominik Lautsch, Robert J Hilkert, Xi Tan, Larry A Allen, Adam D Devore, Brooke Alhanti, Ileana L Pina, Nancy M Albert, Javed Butler, Stephen J Greene
Journal: Circulation (2022)

Background: In January 2021, vericiguat was approved by US FDA to reduce the risk of cardiovascular death and HF hospitalization following a recent worsening HF event based on results of the VICTORIA trial. Limited data are available characterizing generalizability to US clinical practice. Methods: We studied patients hospitalized with HF with reduced ejection fraction (HFrEF) &lt;45% across 525 sites in the Get With The Guidelines (GWTG)-HF registry between January 2014 - December 2020. We excluded patients who left against medical advice, transferred to an acute care facility or to hospice care, or had missing critical data elements. We applied approximate FDA label criteria (excluding eGFR&lt;15 mL/min/1.73 m 2 , dialysis, or heart transplantation or mechanical circulatory support) and eligibility criteria of the VICTORIA trial to the GWTG-HF sample. Results: Among 241,057 patients with EF&lt;45% in GWTG-HF, 221,730 (92%) could be candidates for vericiguat under the FDA label and 92,249 (38%) would have been eligible for VICTORIA. The most frequent reason for ineligibility in the FDA label was eGFR&lt;15 mL/min/1.73 m 2 (n=13,747; 5.7%). Sex, race, and clinical characteristics were generally similar between GWTG-HF registry participants, FDA label candidates, and VICTORIA trial eligible patients ( Table ). Among patients age ≥65 years linked to Medicare, 12-month mortality, HF hospitalization, and all-cause hospitalization were similar across the three groups. Conclusions: These data from a large US hospitalized HF registry suggest that more than 9 out of 10 patients hospitalized for HFrEF may be candidates for vericiguat based on the FDA label. Patients meeting and not meeting VICTORIA trial eligibility criteria had similar characteristics and outcomes, supporting generalizability of the FDA label and the VICTORIA trial to US practice. Medicare beneficiaries hospitalized for HFrEF and eligible for vericiguat face high post-discharge mortality and readmission rates.
Abstract 11054: Switching From Dual Antiplatelet Treatment Regimens With Aspirin Plus a P2Y <sub>12</sub> Inhibitor to Dual Pathway Inhibition With Low-Dose Rivaroxaban in Adjunct to Aspirin in Patients With Coronary Artery Disease: The SWAP-AC Study
Authors: Luis G. Ortega-Paz, Fabiana Rollini, Mattia Galli, Latonya Been, Ghussan Ghanem, Awss Shalhoub, Tiffany Ossi, Andrea Rivas, Xuan Zhou, Andres Pineda, Siva Suryadevara, Daniel Soffer, Martin Zenni, Dominick J Angiolillo, Francesco Franchi
Journal: Circulation (2022)

Introduction: Dual antiplatelet therapy (DAPT) and dual pathway inhibition (DPI) are potential long-term antithrombotic strategies for patients with coronary artery disease (CAD). However, patients already on DAPT are most likely to remain on the same treatment regimen rather than switching. To date, there is no data on the feasibility of switching from DAPT to DPI and the pharmacodynamic (PD) effects of such approach. Methods: SWAP-AC was a prospective, randomized, PD study conducted in 90 patients with CAD on DAPT with aspirin (81mg/qd) plus a P2Y 12 inhibitor [clopidogrel (75 mg/qd; n=30), ticagrelor (90mg/bid; n=30), or prasugrel (10mg/qd; n=30)]. Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81mg/qd plus rivaroxaban 2.5mg/bid). PD assessments included VerifyNow P2Y 12 reaction units (PRU), light transmittance aggregometry (LTA) using 20 μM ADP, tissue factor (TF), and a combination of collagen + 5 μM ADP + TF (CATF, a marker of platelet-mediated global thrombogenicity), and a thrombin generation (TG) assay. Assays were performed at baseline (on DAPT) and 30 days post-randomization [trough (before maintenance dose) and peak (2 hours after maintenance dose) levels]. Results: Switching from DAPT to DPI occurred without side effects. TG was reduced with DPI. In each cohort, DAPT was associated with lower PRU levels than DPI ( Figure ); LTA following ADP stimuli showed consistent results (data not shown). LTA following CATF stimuli (primary endpoint) showed no differences between DPI and DAPT in the ticagrelor and prasugrel, but not clopidogrel, cohorts ( Figure ). There were no differences in any of the cohorts with LTA using TF. Conclusions: SWAP-AC is the first study supporting the feasibility of switching to DPI patients with CAD on different maintenance DAPT regimens. Such approach was associated with increased P2Y 12 reactivity but reduced thrombin generation with a limited impact on platelet-mediated global thrombogenicity.
Abstract 12122: Five-Year Serial Measurement of the Intermountain Mortality Risk Score for Population Health Assessment Reveals Personalized Temporal Trajectories of Differential Longevity Over Two Decades
Authors: Benjamin D Horne, Joseph R Bledsoe, Joseph B Muhlestein, Scott C Woller, Kirk U Knowlton, Sarah Majercik, Tami L Bair, Gregory L Snow, James F Lloyd, Viet T Le, Sterling T Bennett, Brianna S Ronnow, Heidi T May, Jeffrey L Anderson
Journal: Circulation (2022)

Introduction: Health, wellness, and healthcare are most effectively and efficiently managed when health status is quantitatively measured. The Intermountain Mortality Risk Score (IMRS) is a well-validated low-cost decision tool calculated from the complete blood count and basic metabolic profile that can be electronically deployed to inform clinician or patient actions. This study evaluated if 3 serial IMRS measurements improved mortality prediction. Methods: In 119,379 Intermountain Healthcare outpatients, inpatients, and emergency patients, baseline (BL) IMRS was calculated in 1999-2005. Of those, the following were excluded: 22,678 who died prior to having 3 IMRS measurements and 38,228 survivors who at 5 years (y) post-BL did not have 3 IMRS. In the study cohort of 58,473 patients, a 1 st follow-up (1F) IMRS was available 1.49±0.79 y post-BL (range 1-4 y), and a 2 nd follow-up (2F) IMRS at 3.75±0.80 y post-BL (range 2-5 y). Patients had 13.4±1.7 y of follow-up after 2F (range: 9.3-18.7 y), with total follow-up post-BL of 17.2±1.5 y (range: 14.3-20.7 y). Results: Overall, 26,693 patients died (45.7%) after 2F. In females, IMRS for decedents vs. survivors was, respectively, 11.3±3.9 vs 6.3±4.0 at BL, 11.1±3.9 vs 5.7±4.0 at 1F, and 12.2±4.2 vs 6.1±4.0 at 2F; differences in males were similar to those results (all p&lt;0.001). Relative risks for IMRS categories are shown in the Table. C-statistics for females were c= 0.815, 0.834, 0.858 for BL, 1F, and 2F, with 0.872 for a sum of the 3 IMRS (results were similar for males, with absolute c 0.06-0.08 lower). Conclusions: IMRS predicted substantial risk differences at each of 3 timepoints, but the IMRS trajectory (including declines in IMRS) revealed by the sequence of IMRS measurements better personalized risk assessment. When risk level and direction are considered together, critical junctures in a person’s health journey may be revealed, empowering earlier or more intensive prevention, diagnostic testing, and interventions.
Abstract 11841: Activation of Cardiac Fibulin-4 Protects Against Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure
Authors: Elza van Deel, Nicole van Vliet, Thierry van den Bosch, Ariane van Spreeuwel, Noortje Bax, nicky boontje, Takako Sasaki, Jolanda Van Der Velden, C Bouten, Jan von der Thüsen, Jan H Danser, Dirk J Duncker, Ingrid Van Der Pluijm, Jeroen Essers
Journal: Circulation (2022)

Cutis laxa is a rare disorder caused by mutations in the extracellular matrix (ECM) protein Fibulin-4 and patients are susceptible to stress-induced cardiac dysfunction. Mice with a 75% reduction in Fibulin-4 expression (Fibulin-4 R/R ) developed cardiac hypertrophy, dilation and dysfunction as well as aortic aneurysms. The prevailing view is that this is the result of aortic and/or valvular disease, given that Fibulin-4 is believed to be exclusively involved in arterial and valvular elastogenesis and collagen deposition. Yet mortality after cardiac pressure-overload through transverse aortic constriction (TAC) was also increased in haploinsufficient Fibulin-4 +/R mice with a 50% reduced Fibulin-4 expression compared to wildtype animals. To determine whether the TAC-induced dilated cardiomyopathy in haploinsufficient Fibulin-4 +/R mice is a primary manifestation resulting from ECM abnormalities we analyzed the hearts of these mice for the presence of Fibulin-4 expression. Fibulin-4 expression was found to be activated throughout the entire myocardium in TAC-exposed wildtype animals. TAC-exposed Fibulin-4 +/R animals did not show this strong increase in myocardial Fibulin-4 expression but displayed emergence of altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including decreased focal adhesion kinase activity similar to TAC-exposed wildtype animals. Moreover, reduced Fibulin-4 expression aggravated TAC-induced cardiac fibrosis and pulmonary congestion. In microtissues derived from neonatal Fibulin-4 deficient hearts, Fibulin-4 deficiency decreased the beating frequency and contractile force of microtissues. It also reduced the maximal force-generating capacity of single membrane-permeabilized cardiomyocytes. Our findings demonstrate novel functions for Fibulin-4 in cardiac homeostasis, and show that reduced Fibulin-4 expression drives myocardial disease in response to cardiac pressure overload independent of aortic valvular pathology. These so far unrecognized effects of Fibulin-4 on myocardial function could have important implications both for patients with connective tissue disorders and for the general population in response to pressure overload.
Abstract 11968: Association Between Reduction in Inflammation and Change in Cardiovascular Risk: Results From the Liira Study
Authors: Brittany N Weber, Dana Weisenfeld, Thany Seyok, Elena Massarotti, Leanne Barrett, Daniel Solomon, Jorge Plutzky, Marcy Bolster, MARCELO DI CARLI, Katherine P Liao
Journal: Circulation (2022)

Background: Coronary microvascular disease (CMD) is associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). Studies suggest that higher RA disease activity is associated with a higher degree of CMD, as measured by coronary flow reserve (CFR). However, it is not known whether reducing inflammation results in improvement in CMD or other CV correlates. The objective of this study was to determine the association between reducing inflammation with changes in CV risk. Methods: The Lipids, Inflammation and CV risk in RA (LiiRA) study recruited RA patients age ≥18 yrs with active RA about to initiate a TNFi as part of clinical care. All subjects underwent a stress myocardial perfusion PET scan to quantify CFR at baseline and after 24 weeks. A lower CFR in the absence of obstructive CAD is indicative of CMD, CFR&lt; 2.5 defined CMD. Inflammatory markers and hs-cTnT were performed at baseline and 24 weeks. Primary and secondary outcomes was change in CFR and hs-cTnT, respectively, and tested by Spearman correlations. Results: A total of 66 subjects completed the study, 80% female, mean RA duration 7.7 yrs. Baseline estimated ASCVD risk was 5.6%, yet 47% had evidence of CMD. We observed a significant reduction in all inflammatory markers between baseline and follow-up, along with improvements in RA disease activity; however, no change in the mean CFR or hs-cTnT was observed. A reduction in hsCRP and IL-1beta was associated with a reduction in hs-cTnT. A non-significant trend for correlation of reduced IL-1beta with higher CFR was observed among subjects with CMD at baseline (Figure). Conclusion: There was a high prevalence of CMD at baseline, but CFR did not significantly improve. Reducing inflammation was correlated with improvements in measures of CV risk, mainly in the subset of patients with detectable hs-cTnT, particularly via the IL-1beta pathway. These data suggest that hs-cTnT may be a useful marker when considering targeting inflammation to reduce CV risk in RA.